The current proposal from Mayo Clinic is for continued support as a participating clinical center (PCC) for the NIDDK supported HALT-PKD clinical trials. The Mayo Clinic is one of the four PCCs participating in HALTPKD and has established a consortium with the University of Kansas Medical Center and with the Cleveland Clinic. Despite substantial data that implicate the renin-angiotensin system in the pathogenesis of ADPKD, no large randomized trial to determine the effectiveness of its blockade of has been done. HALT-PKD comprises two 5-year double-blind randomized trials. Studies A and B test the hypothesis that intensive combined blockade using an angiotensin-converting enzyme inhibitor (ACE-I) together with an angiotensin receptor blocker (ARB) in hypertensive (>130/80 mm Hg) people with ADPKD delays disease progression more effectively than ACE-I monotherapy, independent of the level of BP control. Study A also examines whether lower BP delays progression early in the course of disease. Subjects with a GFR>60 mL/min/1.73 m2 will be randomized in Study A to either ACE-I/ARB therapy or ACE-I monotherapy, and either low (systolic 95-110/diastolic 60-75 mm Hg) or standard (systolic 120-130/diastolic 70-80 mm Hg) BP. The primary outcome is the percent change in total kidney volume measured by MRI. Secondary measures include LV mass index and renal blood flow (by MR), albumin excretion, and GFR. Subjects with GFR 25-60 ml_/min/1.73 m2 will be randomized in Study B to ACE-I/ARB therapy versus ACE-I monotherapy (all standard BP). The primary outcome is the time to a composite of doubling of serum creatinine, ESRD or death. In both studies BP is assessed by home blood pressures. A total of 548 participants for Study A and 470 for Study B will provide 90% power to detect 25% differences in treatment arms of each study. A stepwise protocol of increasing doses of lisinopril and telmisartan/placebo followed by stepwise addition of other agents is used to achieve BP targets. Between March 2006 and January 2008, 600 patients have been randomized (210 at this PCC), 205 have completed one year (89 at this PCC), and 73 (34 at this PCC) have completed 18 months of follow-up. Mean BPs have been mostly on target and excellent separations in systolic, diastolic and mean BPs and medication steps have been achieved between the standard and the low BP arms of Study A. It is expected that enrollment will be completed by the end of 2008. This PCC plans to enroll 334 participants (188 at the Mayo Clinic, 86 at KUMC and 60 at the Cleveland Clinic). This represents an over-recruitment of 79 patients and will help to achieve the overall recruitment target.